Platelets, as well as erythrocytes and neutrophils which are also in the class of mature corpuscles, originate from hematopoietic stem cells and are produced by the differentiation and proliferation of these cells. In the early stage of the hematopoietic process, hematopoietic stem cells differentiate and proliferate to megakaryocytes via their precursor cells. Mature magakaryocytes form proplatelets which would eventually be released into peripheral blood as platelets. It has been found that various hematopoietic factors and cytokines are involved in the series of steps in the above-described platelet production process. For example, it has been shown experimentally that interleukin-3 is involved in the stage from stem cells to megakaryocytes, interleukin-6 in the maturing of megakaryocytes and thrombopoietin in the stage from stem cells to the maturing of megakacyocytes. It is speculated that a certain factor is also involved in the process of platelet production and release from mature magakacyocytes but no such factors are yet to be identified.
Thrombocytopenia manifests itself if either one of the steps in the above-described thrombopoietic process is interfered with and there are two major causes of such interference, abnormality in hematopoietic cells and abnormality in hematopoietic factors. In the first case, the differentiation and proliferation of hematopoietic cells are interfered with by either congenital or acquired causes. Aplastic anemia and osteomyelodysplasia syndrome are known to occur by congenital causes and bone marrow transplantation and the administration of chemotherapeutics are two known acquired causes. As for the abnormality in hematopoietic factors, cyclic thrombocytopenia is known to be caused by this reason.
Transfusion of platelets is currently considered to be an effective means of treating thrombocytopenia but this treatment does not necessarily supply an adequate amount of platelets and, in addition, it involves the risk of infection with viruses and other pathogens. Therefore, the development of agents effective in preventing and treating thrombocytopenia is desired.
A parathyroid hormone (PTH) is known as one of the important hormones for bone metabolism. Numerous reports have so far been published to describe the actions of PTH on the bone but there are few reports on its action on the hematopoietic system. The exception is the report by Meytes et al (J. Clin. Invest. Vol. 67, 1263-1269:1981), which showed that PTH interfered with the in vitro colony formation by BFU-E (precursor cells of erythrocytes) and CFU-GM (precursor cells of granulocytes and macrophages). Thus, nothing has been unraveled about the action of PTH on thrombopoiesis.